SIBO

Introduction
According to most research, a relatively rare condition in cats with gastro-intestinal (GI) disease, Small Intestinal Bacterial Overgrowth (SIBO) is not an easy condition to recognize, diagnose, treat, or permanently eliminate. It is now beginning to be called SID (small intestinal dysbiosis), dysbiosis meaning microbial imbalance, as it is felt that this more accurately describes the condition. In dogs, it has also been called ARD, Antibiotic Responsive Diarrhea. I generally will refer to it here as SIBO.

What is SIBO?
It is, as the SIBO name says, an overgrowth of bacteria in the small intestine. However, it is not an invasion by parasites or invading bacteria which can create an infectious response. It is rather a case where normally resident bacteria of the small intestine over-breed and create problems related to that overgrowth. “The upper small intestine is supposed to be relatively sterile, and increased numbers of bacteria have been incriminated as a cause of intestinal dysfunction. This process has been called “small intestinal bacterial overgrowth” (SIBO), and is likely to occur secondary to partial obstructions, blind loops and exocrine pancreatic insufficiency (EPI), when bacteria can accumulate and ferment undigested food. Yet an idiopathic form of SIBO has been claimed in large breed dogs, especially young German shepherd dogs. The belief now is that true overgrowth does not exist in this syndrome, and that a more accurate term is “antibiotic-responsive diarrhea” (ARD) because it is characterized by the positive response to antibiotic therapy.” 1 In other words, it’s uncertain exactly what is going on, let alone why.

What triggers the overgrowth?
There isn’t a lot of research about SIBO specifically in cats; most research is either about humans or dogs. One possible contributor in SIBO may be slower than normal motility, the natural rhythmic action of the bowel which moves food from the stomach through the intestine to eventual elimination at the anus. Structural issues in the bowel can be a factor, such as an obstruction or trauma. Allergies to food ingredients could play a role. Inflammatory Bowel Disease (IBD) is certainly a risk factor. Deficiencies in acidity of the bowel environment, or deficiencies in digestive enzymes from the pancreas due to pancreatitis or exocrine pancreatic insufficiency, as well as extensive antibiotic use which changes the mucosal lining of the intestine – all may be factors in the development of bacterial overgrowth. Does SIBO trigger GI diseases like IBD or pancreatitis, or do they trigger bacterial overgrowth in the small intestine? The answer may be yes to both questions, as the GI system is intricate and intertwined. It may be that SIBO is unrecognized and undiagnosed simply because the issues with IBD, pancreatitis and/or liver disease are so pervasive that all energy goes into diagnosing and managing those diseases, without recognition that SIBO may be a significant contributing factor in the management of them.

Symptoms of SIBO
There are no unique symptoms that point to SIBO directly, and they can be lacking entirely, especially in the early stages of SIBO and other gastric diseases. Noticeable symptoms include weight loss and changes in stool including diarrhea, especially if odorous and paler in color (which is indicative of digestive or malabsorption issues), gas or gurgling in the bowel. These particular symptoms are more indicative of SIBO than is appetite loss (anorexia) or vomiting, or voracious appetite. These last may occur as a by-product of other gastric issues concurrent with SIBO. But as almost all of these symptoms fit so many other GI diseases – IBD, pancreatitis, hepatic liver disease, gall bladder or bile duct issues, as well as exocrine pancreatic insufficiency (EPI), it’s entirely understandable why small intestinal bacterial overgrowth isn’t an automatic assumption. SIBO is not something that veterinarians will immediately suspect, and perhaps many of them have not seen an actual case in their practice.

How is SIBO diagnosed?
Furthering the challenge of diagnosing SIBO is that there is no specific blood or fecal test that definitively proves a bacterial overgrowth. Diagnosis is often a matter of ruling other conditions out, as much as ruling SIBO in. Negative fecal tests will rule out normal parasitic culprits for diarrhea, for example, but these have no specific pointers to any of the gastric diseases. Normal serums in the blood chemistry panel likewise have no markers for SIBO.

While there are tests for SIBO in humans, these are either not feasible or desirable for animals. Breath analysis and sampling duodenal fluid from the small intestine are two such examples. Neither cats nor dogs will blow into a tube, making collection of a sample difficult and not especially clean. Samples of fluid from the small intestine would require an endoscopy under anesthesia, which makes it more expensive and riskier to the animal. “… the technique of bacterial quantitation of duodenal juice is so difficult and prone to error, not to mention labor-intensive and expensive, that it is not a technique that should be contemplated in practice.” 2

The most commonly used diagnostic for SIBO are two of the four blood serum tests in the GI panel 2, from Texas A&M.
– TLI – which tests for exocrine pancreatic insufficiency (EPI)
– Spec fPL – which tests for pancreatitis
– Cobalamin (B12) levels
– Folate levels

TLI checks for exocrine pancreatic insufficiency, where the pancreas does not produce and/or release enough digestive enzymes into the intestine to properly digest food. EPI may be caused by issues with the pancreas, or with the bowel itself, perhaps due to IBD. There is some speculation that EPI may be a direct cause of SIBO. The spec fPL is the specific test for feline pancreatitis.

The other two tests in the GI Panel 2 are B12 and folate which are how SIBO is most often diagnosed, by comparison of their respective serum levels. “Other less complicated and less accurate diagnostic methods are available to detect bacterial proliferation in the small intestine. Serum folic acid levels may increase in dogs with SIBO because numerous bacteria synthesize folic acid. On the other hand, serum vitamin B12 (cobalamin) concentration is often decreased in association with intestinal malabsorption.”3 Hence with SIBO, cobalamin levels are typically down while folate levels are up.

The following table from Dr Newman’s article “Selected Diseases of the Small Intestine Cause Vomiting and/or Diarrhea” 4 illustrates the relationship between the two substances with interpretation as primary location of the condition.

Note: it is important that the cat has been fasted for 12-hours prior to the blood draw for any of the tests in the GI Panel 2.
Note: supplementation of B12 may show higher cobalamin levels, so that SIBO could still be an issue where B12 and folate both show high results. Folate supplementation should also be considered.

Treatment of SIBO
Typically, the treatment for SIBO is with antibiotics or antimicrobials to control the overgrowth. Metronidazole and tylosin (Tylan) are the most commonly used, although others such as amoxicillin may also be used. “Recently conducted studies have indicated that tylosin causes wide resistance to antibiotics in the intestine (unpublished results). 5 Tylosin also may affect the serum values for the liver, including the ALT. metronidazole also has some risk of toxicity in the liver. “In retrospect, looking up the side effects of metronidazole, a rare side effect is built-up toxicity from it, of which Sasha had the exact symptoms – vomiting, unable to walk or stand, disorientation, the eyes rolling. Time and Valium is the antidote.”6 It is for this reason that it is generally recommended for shorter term use, particularly in animals with liver disease. However, the length of treatment is dependent on the severity of SIBO in the animal, and often will be life-long, as even if treatment is successful, the overgrowth often returns. So it may be necessary to treat using such drugs, despite any possible risk. Many veterinarians have prescribed metronidazole many times with no adverse side-effects, but they can occur.

Treatment of other symptoms follows the usual protocols for IBD or pancreatitis: managing diarrhea, controlling any vomiting or nausea, ensuring hydration, adequate food and caloric intake. SIBO may be the cause, or simply contributing, to such symptoms, particularly diarrhea. It is important to ensure that B12 levels are kept in the upper-mid range. “Insufficient B12 levels will invite SIBO. Be sure to keep B12 levels at upper mid-range.”7

Brief history of my cat with SIBO
My cat Boston was initially diagnosed with SIBO in 2012 as well as triaditis (IBD, cholangitis and pancreatitis). The diagnosis of SIBO was made because his B12 was well below normal and his folate was very, very high. He showed no symptoms from the SIBO, specifically no diarrhea. Boston was on metronidazole until I chose to stop it in 2014 over my concerns with possible liver toxicity. I forgot that he had SIBO; basically I did not understand what it was and that it was why he was being treated with metronidazole.

Forward to February 2015, Boston had symptoms of increasing diarrhea with stool color becoming paler, yellow-orange. This is a sign of malabsorption, as well as a symptom of EPI and/or more severe IBD. He was also experiencing gradual weight loss from September 2014, though at nearly 19 pounds, this wasn’t of immediate concern. The TLI test in February 2015 indicated no EPI, and the spec fPL showed low-grade pancreatitis as well. His cobalamin was mid-range normal, due to on-going though somewhat infrequent supplementation every 8-12 weeks. However, his folate level was above measurable range, quite high at >24.0.

In the nine months since re-diagnosis of SIBO, Boston was briefly treated with amoxicillin, before settling on metronidazole. Tylosin was ruled out as an option. He has been on Cisapride and prednisolone since 2012 for IBD. His diarrhea worsened with the amoxicillin and little or no change to the serum levels was seen. He’s now on 50mg metronidazole daily, which at least hasn’t made his diarrhea worse, though neither has it resolved it. His folate has yet to drop down to the measurable range, let alone normal range. It has been >24.0 consistently; normal range is 5.9 to 19.9 ug/L.

In October, he lost nearly a pound (.9#) in just three weeks, despite eating voraciously (a symptom of EPI). Re-ran the GI Panel; TLI was in the normal range. His chronic pancreatitis had abated. B12 was slightly lower though still in normal, and folate was again >24.0.

After 6 weeks, the increase in prednisolone has not made any significant difference. It does seem likely that his IBD has worsened likely in the Large Intestine, since he never had diarrhea when first diagnosed with SIBO three years ago, but it has been worsening since SIBO was re-diagnosed. Broadly speaking, a healthy large bowel can cope with bacterial overgrowth and the like without developing diarrhea. Because of the likelihood of worsening IBD, we plan to begin treatment with Leukeran in the near future.

Also, there is some thought that damage to his pancreas may be affecting its ability to provide the necessary enzymes for proper digestion, hence malabsorption and the yellow-orange color of his stool. We may put him on animal-based pancreatic enzymes despite the EPI test being normal. This would be after Leukeran is successfully introduced and any results noted. In the meantime, plant-based digestive enzymes have just been re-started, though it is too early to see any effect.

Conclusion
Small intestinal bacterial overgrowth is a rarely diagnosed condition in cats, for various reasons. However it is worth keeping in mind when trying to determine what might be causing long-duration gastro-intestinal issues such as on-going diarrhea that doesn’t respond to treatment, or that consistently returns despite ‘successful’ treatment. This is a condition which seems to be common for some cats with IBD, yet they aren’t diagnosed with SIBO. It may be that the full GI Panel isn’t often run, but only single tests from it, for pancreatitis, or EPI, or B12 deficiency. The GI Panel is the most commonly used diagnostic tool, because it’s the most affordable and easiest to administer. The comparison of B12 and folate values is how SIBO is most often diagnosed. The GI panel is useful for establishing initial baseline values, not only for folate and B12, but for other major gastric diseases like pancreatitis and exocrine pancreatic insufficiency, both of which are linked to SIBO. Small Intestinal Bacterial Overgrowth is a challenging condition in all respects.